Variant1: NM_000257.4(MYH7):c.1633G>A (p.Asp545Asn)

ClinVar: 264607 https://www.ncbi.nlm.nih.gov/clinvar/variation/264607/

gnomAD: 0.00001759, https://gnomad.broadinstitute.org/variant/14-23897049-C-T

Variant2: NM_000257.4(MYH7):c.2678C>T (p.Ala893Val)

ClinVar: 177763 https://www.ncbi.nlm.nih.gov/clinvar/variation/177763/

gnomAD: Not in gnomAD

Variant3: NM_000257.3:c.2713T>C (p.Cys905Arg)

CAID: CA389047302 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.2713T%3EC

gnomAD: Not in gnomAD

Variant4: NM_000257.4(MYH7):c.2863G>A (p.Asp955Asn)

ClinVar: 264608 https://www.ncbi.nlm.nih.gov/clinvar/variation/264608/

gnomAD: Not in gnomAD

Variant5: NM_000257.3:c.415G>T (p.Val139Leu)

CAID: CA389052864 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.415G%3ET

gnomAD: Not in gnomAD

Variant6: NM_000257.4(MYH7):c.495G>A (p.Met165Ile)

ClinVar: 524948 https://www.ncbi.nlm.nih.gov/clinvar/variation/524948/

gnomAD: Not in gnomAD

Variant7: NM_000257.3:c.547G>A (p.Gly183Arg)

CAID: CA389052574 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.547G%3EA

gnomAD: Not in gnomAD

Variant8: NM_000257.3:c.5754C>G (p.Asn1918Lys)

CAID: CA389034544 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.5754C%3EG

gnomAD: Not in gnomAD

Variant9: NM_000257.3:c.5773C>G (p.Arg1925Gly)

CAID: CA257807342 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.5773C%3EG

gnomAD: Not in gnomAD

Variant10: NM_000257.4(MYH7):c.689T>C (p.Phe230Ser)

ClinVar: 263543 https://www.ncbi.nlm.nih.gov/clinvar/variation/263543/

gnomAD: Not in gnomAD

Variant11: NM_000257.3:c.715_717del (p.Asp239del)

CAID: CA913184869 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.715_717del

gnomAD: Not in gnomAD

Variant12: NM_000257.4(MYH7):c.732+1G>A

ClinVar: 14127 https://www.ncbi.nlm.nih.gov/clinvar/variation/14127/

gnomAD: 0.00005437, https://gnomad.broadinstitute.org/variant/14-23900793-C-T

Variant13: NM_000257.3:c.798T>A (p.Tyr266Ter)

CAID: CA389052023 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.798T%3EA

gnomAD: Not in gnomAD

Variant14: NM_000257.4(MYH7):c.847T>G (p.Tyr283Asp)

ClinVar: 66081 https://www.ncbi.nlm.nih.gov/clinvar/variation/66081/

gnomAD: Not in gnomAD

Variant15: NM_000257.3:c.902T>A (p.Leu301Gln)

CAID: CA389051788 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000257.3%3Ac.902T%3EA

gnomAD: Not in gnomAD

Supplementary Data: Online Table 2a

Case:

CasePreviousTesting: Full sarcomere testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), Additional testing (ABCC9, ACTN2, ANKRD1, BAG3, CALR3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, GLA, JPH2, JUP, LAMA4, LAMP2, LMNA, MYH6, MYPN, MYOZ1, MYOZ2, PKP2, PLN, PRKAG2, RBM20, RYR2, SCN5A, SGCD, TAZ, TCAP, TMEM43, TNNC1, TTN, VCL and LDB3)

CaseGenotypingMethod: DNA isolated from peripheral blood, targeted enrichment, next-gen sequencing with panel of 46 genes

Variant: NM_000257.3(MYH7):c.732+1G>A

ClinVar: 14127, https://www.ncbi.nlm.nih.gov/clinvar/variation/14127/

gnomAD: 0.000003976, https://gnomad.broadinstitute.org/variant/14-23900793-C-T

Supplementary Data: Online Table 1a

Case:

CasePreviousTesting: Full sarcomere testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), Additional testing (ABCC9, ACTN2, ANKRD1, BAG3, CALR3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, GLA, JPH2, JUP, LAMA4, LAMP2, LMNA, MYH6, MYPN, MYOZ1, MYOZ2, PKP2, PLN, PRKAG2, RBM20, RYR2, SCN5A, SGCD, TAZ, TCAP, TMEM43, TNNC1, TTN, VCL and LDB3)

CaseGenotypingMethod: DNA isolated from peripheral blood, targeted enrichment, next-gen sequencing with panel of 46 genes

Variant: NM_000257.3(MYH7):c.732+1G>A

ClinVar: 14127, https://www.ncbi.nlm.nih.gov/clinvar/variation/14127/

gnomAD: 0.000003976, https://gnomad.broadinstitute.org/variant/14-23900793-C-T

Case120682: 62 year old Caucasian female

DiseaseAssertion: LVNC

FamilyInfo: family history was negative for cardiomyopathy or CHF, one daughter was noted to have a persistent high resting pulse

CasePresentingHPOs:

CaseHPOFreeText: first degree AV-block on ECG and prominent trabeculations at the left ventricular (LV) apex, mild aortic regurgitation

CaseNotHPOs:

CaseNotHPOFreeText:pulmonary hypertension

CasePreviousTesting: 41 cardiomyopathy-associated genes

GenotypingMethod: next generation sequencing and variant analysis, WES or WGS

Variant: NM_000257.4:c.732+1G>A

ClinVar: 14127

CAID: CA016715

gnomAD: 0.00005437 East Asian

https://gnomad.broadinstitute.org/variant/14-23900793-C-T